Fabrication technique of micro spray nozzles

ABSTRACT

A method for manufacturing a micro nozzle is disclosed. The method includes the following steps: providing a substrate having a channel for fluids, wherein the thickness of the substrate is D 1  and the depth of the bottom of the channel is D 3 ; forming a protrusion having an acute angle θ on the edge of the substrate through the cutting operation; and further forming a nozzle with a thickness D 2  of on the tip of the protrusion. The outlet of the channel is located on the tip of the protrusion. Moreover, the thickness of the nozzle on the tip of the protrusion is less than the depth of the channel or than the thickness of the substrate. The micro nozzle made by the method illustrated above can provide a reliable and stable interface for electro-spraying.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention is related to a method for manufacturing a micro spray nozzle; more particularly, a method for manufacturing a micro spray nozzle used in a semi-conductor wafer-cutting technique.

2. Description of Related Art

Due to the numerous types of proteins and their complex structures and highly changeable properties, the process of protein analysis is thus very time-consuming and troublesome. However, recent integration of MEMS (Micro Electro Mechanical Systems) technology and biotechnology makes it possible to utilize microfabrication technology to miniaturize traditional analytical instruments, which in turn improves the effectiveness and accuracy of protein analysis. Presently, success has been achieved in exploitation of microfluidic chips which include dialysis processing, chromatography and electrophoresis. Electrospray ionization is a technique that directly transforms proteins in a solution into gas phase protein ions via electrospraying under atmospheric pressure to allow a mass spectrometer to process detection. This technique has been one of the important tools in identifying unknown proteins' chemical structures. Furthermore, microfluidic chips applied in protein purification and separation can further form a simple protein analysis system by connecting to a mass spectrometer via a miniaturized electrospray ionization apparatus. Then the protein analysis can be done consistently.

Different methods can be used in integrating general electrospray nozzles and microfluidic chips due to different materials of the chips. For example, some research utilizing the method of connecting a capillary to a stream pipe involves connecting the microfluidic chips and capillary. Then a voltage is applied on the tip end of the capillary to spray gas phase ions. However, there is still a dead space between the joint of the microfliudic chips and the capillary which affects a comparative trace analyte, influencing its S/N ratio to drop, and even causing the mixing of the analyte that has been separated. Also, prior methods utilize lithography or plasma etching to etch the polymer to become a tip nozzle having a channel for the fluids. Although an effective spray nozzle can be obtained, the manufacturing process requires too much time and effort. Moreover, another method, utilizing mold forming and then assembling, bonds the model of tip nozzle to upper and lower substrates to form a spray nozzle. This method, however, may have the drawback of malpositioning the joint, resulting in poor quality of the products. It is even suggested to adopt to the traditional etching process used in wafer production to etch the wafer to a spray nozzle having micro size. The manufacturing process is however very time-consuming. Furthermore, others directly make the egress of the spray nozzle to be flat instead of displaying an acute angle. When spraying the liquids, the drops easily slide or are affected by the surface tension to spread on the spray nozzle, resulting in poor spraying. In addition, the concept of sacrificial layer in MEMS has been applied. The Parylene polymer is used as the material. The photoresist contained interiorly is released out to form a suspended spray nozzle structure of soft material. The manufacturing is not only complex, but also is time-consuming. From the aforementioned prior techniques, it is known that many problems, such as the dead space of the stream pipe, requiring much time and effort, complex manufacturing, low reliability of the products, and even the economic benefits, require solving.

Therefore, a stable and reliable electrospray interface that is easy to manufacture is in great need to improve the prior drawbacks. The electrospray mass spectrometer to process high throughout trace sample analysis should also be taken into account.

SUMMARY OF THE INVENTION

The present invention discloses a method for manufacturing a micro spray nozzle, comprising the following steps: providing a substrate having at least one channel for fluids; utilizing a cutting tool to cut the substrate, making the substrate form a prism having an angle θ; and utilizing the cutting tool to cut the angle θ of the prism to form a spray nozzle having a thickness of D2, whereby an egress of the channel for fluids is positioned in the spray nozzle.

The thickness of the substrate is D₁. The depth from the bottom of the channel for the fluids to the surface of the substrate is D₃. The angle θ is not greater than 90°. Moreover, the thickness D₂ of the spray nozzle is smaller than the thickness D₁ of the substrate. The depth D₃ of the channel for the fluids is smaller than the thickness D₁ of the substrate.

In the preferable configuration of the present invention, the egress of the channel for the fluids can be positioned on the spray nozzle. In addition, the depth D₃ of the channel for the fluids can be greater than half of the difference between D₁ and D₂. In another preferable configuration, the egress of the channel for the fluids need not be restricted to the spray nozzle, and the depth D₃ of the channel for the fluids can be smaller than half of the difference between D₁ and D₂.

Also, the substrate to be utilized in the present invention can be any prior substrate having a channel for the fluids. The manufacture of the substrate is not restricted, but preferably the substrate is formed by bonding at least two pieces of substrates and comprises a channel for the fluids.

The thickness D₁ of the substrate of the micro spray nozzle according to the present invention is not restricted, but preferably is approximately between 50 μm and 1500 μm. Moreover, the thickness D₂ of the spray nozzle is not restricted, but preferably is approximately between 5 μm and 500 μm.

Furthermore, the aforementioned cutting tool can be any prior cutting tool, but preferably is a wheel knife. The substrate according to the present invention can be made of any material, but is preferably made of silicon, glass, ceramic, polymer, plastics, or a combination of the aforementioned materials. The cross-section of the channel for the fluids according to the present invention can be any prior shape, but is preferably a U-shape, V-shape, square, or semi-circular. The aperture size of the channel for the fluids is not restricted, but is preferably smaller than the thickness D₂ of the spray nozzle. In one configuration, the size of the mentioned angle θ is not restricted, but is preferably approximately between 3° and 88°.

In addition, in one configuration of the present invention, the use of the spray nozzle is not restricted, but preferably it can absorb one liquid, gas, colloid, or their combinations. Also, the spray nozzle can spray or discharge one liquid, gas, colloid, or their combinations. In one preferable configuration, the channel for the fluids contained in the spray nozzle according to the present invention can have the function of chromatography, allowing the sample to be purified, separated, and concentrated in the micro spray nozzle.

Fields of application of the spray nozzle of the present invention are not restricted. The spray nozzle can be used in biomedical examination, protein molecular weight detection, and organic molecule detection-related research fields. It is preferable to be integrated to a electrospray mass spectrometer with the spray nozzle according to the present invention to electrospray ionize the object to be measured to favor the process of test analysis.

The present invention may utilize a prior wafer dicing technique in the semi-conductor manufacturing, aiming to process multi-axis precise cutting of the substrate according to the present invention, to manufacture a micro-sized structure and a fluid spray nozzle. The protruded nozzle resembling a capillary is configured in the tip end of the micro channel for the fluids to favor integration of the micro fluid elements and the electrospray ionization mass spectrometer. This integration step not only can integrate and analyze the purification, concentration, separation and electrospray ionization of the sample, but also can connect to the mass spectrometer to complete the consistent analysis of the ultra-trace, simplifying and speeding up the analytical time of the sample.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a manufacturing flow chart of the micro spray nozzle of one preferred embodiment of the present invention.

FIG. 2 is a lateral diagram of the micro spray nozzle of one preferred embodiment of the present invention.

FIG. 3 is an oblique photograph of the spray nozzle of one preferred embodiment of the present invention under a scanning-type electron microscope.

FIG. 4 is the diagram of the testing result of the micro spray nozzle integrated to the electrospray ionization mass spectrometer according to the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT Preferred Embodiment 1

Please refer to FIG. 1 which is a manufacturing flow chart of the micro spray nozzle of one preferred embodiment of the present invention. First of all, one substrate 10 a having a sample injecting aperture 11 and a substrate 10 b having a channel for fluids 12 are provided, and bonding these two substrates to form a substrate 10 having the sample injecting aperture 11 and the channel for fluids 12. The cross-section of the channel for fluids 12 can be in any shape, but is semi-circular in this preferred embodiment. The thickness of the substrate 10 is not restricted, but is 1.2 mm in this preferred embodiment. Next, a cutting tool is used for semi-conductor wafer-cutting (one wheel knife in this preferred embodiment but not shown in the figure) to cut the substrate 10 to one prism 20 having an angle θ. The angle θ in this preferred embodiment is 30°. Finally, at the point of angle θ of the prism 20, a wheel knife is utilized to cut the substrate 10 from its top and bottom respectively along its vertical axis. In other words, to utilize a wheel knife to cut out a spray nozzle 30 having a thickness of D₂ on the cross-section that is almost orthogonal to the channel for the fluids 12. In this preferred embodiment, the thickness D₂ of the spray nozzle is 281.5 μm and the egress of the channel for fluids 12 is positioned on the spray nozzle 30. The micro spray nozzle of the present invention can be obtained from completing the above steps. FIG. 2 is a lateral diagram of the micro spray nozzle of one preferred embodiment of the present invention, wherein D₁ is the thickness of the substrate; D₂ is the thickness of the spray nozzle; and D₃ is the depth of the channel for fluids.

FIG. 3 shows oblique photography of the spray nozzle of one preferred embodiment of the present invention under a scanning-type electron microscope. From the figure, it is known that the method for manufacturing of the present invention can obtain one protruded spray nozzle with an acute angle. The figure shows that the protruded spray nozzle displays a triangular prism. The egress of the spray nozzle is approximately 50 μm away from the cross-section cut by the cutting tool. It can also be observed from the figure that there is one egress of the channel for the fluids.

Preferred Embodiment 2

This preferred embodiment uses the micro spray nozzle manufactured in preferred embodiment 1 for electrospray ionization of the Green Fluorescent Protein (GFP). After connecting the micro spray nozzle and the mass spectrometer, the molecular weight analysis of the GFP can then be proceeded. First of all, a purified sample GFP protein molecule is provided and placed into a injection syringe. The tip end of the syringe is connected to the sample injecting aperture of the micro spray nozzle by a plastic tube. Applying pressure can immediately inject the sample GFP protein molecules into the micro spray nozzle of the present invention. Although the preferred embodiment uses the injection method with a syringe, the injection of sample shall not be restricted to this method only. In this preferred embodiment, the spray nozzle of the present invention connects to a mass spectrometer. One voltage is applied to the egress of the spray nozzle. The liquid phase protein molecules in the egress of the spray nozzle are transformed into gas phase protein ions through the electrospray process, and then sprayed into the mass spectrometer for analysis. The electrospray ionization mass spectrometer used in this preferred embodiment is modeled MicroMass. The condition for the GFP sample to be tested/examined is that its concentration is 10 fmole. Please refer to FIG. 4 for the result of the mass spectrometer analysis. It is apparent from the figure that the experiment obtains a stable signal of the GFP protein molecule, and clearly points out the distribution of its molecular weight. Therefore, the preferred embodiment proves that the micro spray nozzle of the present invention can indeed integrate to the electrospray ionization mass spectrometer. It also proves that the micro spray nozzle can effectively transform the protein molecules in solutions into gas phase protein ions to allow the mass spectrometer to process detection, and to obtain stable detecting signals.

Although the present invention has been explained in relation to its preferred embodiment, it is to be understood that many other possible modifications and variations can be made without departing from the spirit and scope of the invention as hereinafter claimed. 

1. A method for manufacturing a micro spray nozzle, comprising the following steps: providing a substrate having at least one channel for fluids, wherein the thickness of the substrate is D₁, and the depth from the bottom of the channel for fluids to the surface of the substrate is D₃; utilizing a cutting tool to cut the substrate, forming a prism having an angle θ, wherein the angle θ is not greater than 90°; and utilizing the cutting tool to cut the angle θ of the prism to form a spray nozzle having a thickness of D_(2,) whereby an egress of the channel for fluids is positioned in the spray nozzle; wherein the thickness D₂ of the spray nozzle is smaller than the thickness D₁ of the substrate; the depth D₃ of the channel for the fluids is smaller than the thickness D₁ of the substrate.
 2. The method for manufacturing a micro spray nozzle as claimed in claim 1, wherein the depth D₃ of the channel for the fluids is greater than the half value of the difference between D₁ and D₂.
 3. The method for manufacturing a micro spray nozzle as claimed in claim 1, wherein the substrate is formed by bonding at least two pieces of substrates.
 4. The method for manufacturing a micro spray nozzle as claimed in claim 1, wherein the thickness D₁ is approximately between 50 μm and 1500 μm.
 5. The method for manufacturing a micro spray nozzle as claimed in claim 1, wherein the thickness D₂ is approximately between 5 μm and 500 μm.
 6. The method for manufacturing a micro spray nozzle as claimed in claim 1, wherein the angle θ is approximately between 3° and 88°.
 7. The method for manufacturing a micro spray nozzle as claimed in claim 1, wherein the cross-section is U-shape, V-shape, square, or semi-circular.
 8. The method for manufacturing a micro spray nozzle as claimed in claim 1, wherein the cutting tool is a wheel knife.
 9. The method for manufacturing a micro spray nozzle as claimed in claim 1, wherein the material of the substrate can be silicon, glass, ceramic, polymer, plastics, or a combination of the aforementioned materials.
 10. The method for manufacturing a micro spray nozzle as claimed in claim 1, wherein the spray nozzle is used to absorb one liquid, gas, colloid, or their combinations.
 11. The method for manufacturing a micro spray nozzle as claimed in claim 1, wherein the spray nozzle is used to spray or discharge one liquid, gas, colloid, or their combinations.
 12. The method for manufacturing a micro spray nozzle as claimed in claim 1, wherein the spray nozzle is integrated to a electrospray mass spectrometer. 